Ivermectin inhibits the sporogony of Plasmodium falciparum in Anopheles gambiae

Background: When ingested in a blood meal, ivermectin has been shown to reduce the survivorship of Anopheles gambiae in the laboratory and field. Furthermore, ivermectin mass drug administrations in Senegal have been shown to reduce the proportion of Plasmodium falciparum-sporozoite-containing An. gambiae. This study addresses whether ivermectin inhibits sporogony of P. falciparum in An. gambiae. Methods: Anophele gambiae s.s. G3 strain were fed two concentrations of ivermectin (LC25 and LC5) along with P. falciparum NF54 in human blood meals at staggered intervals. Mosquitoes ingested ivermectin concurrent with parasites (DPI 0), or at three (DPI 3), six (DPI 6), and nine (DPI 9) days post parasite ingestion, or three days prior (DPI -3) to parasite ingestion. Mosquitoes were dissected at seven, twelve or fourteen days post parasite ingestion and either oocyst or sporozoite prevalence was recorded. To determine if P. falciparum sporozoite-containing An. gambiae were more susceptible to ivermectin than uninfected controls, survivorship was recorded for mosquitoes which ingested P. falciparum or control blood meal on DPI 0 and then a second blood meal containing ivermectin (LC25) on DPI 14. Results: Ivermectin (LC25) co-ingested (DPI 0) with parasites reduced the proportion of An. gambiae that developed oocysts (chi(2) = 15.4842, P = 0.0002) and sporozoites (chi(2) = 19.9643, P < 0.0001). Ivermectin (LC25) ingested DPI 6 (chi(2) = 8.5103, P = 0.0044) and 9 (chi(2) = 14.7998, P < 0.0001) reduced the proportion of An. gambiae that developed sporozoites but not when ingested DPI 3 (chi(2) = 0.0113, P = 1). Ivermectin (LC5) co-ingested (DPI 0) with parasites did not reduce the proportion of An. gambiae that developed oocysts (chi(2) = 4.2518, P = 0.0577) or sporozoites (chi(2) = 2.3636, P = 0.1540), however, when ingested DPI -3 the proportion of An. gambiae that developed sporozoites was reduced (chi(2) = 8.4806, P = 0.0047). Plasmodium falciparum infection significantly reduced the survivorship of An. gambiae that ingested ivermectin (LC25) on DPI 14 compared to control mosquitoes that ingested a primary blood meal without parasites (chi(2) = 4.97, P = 0.0257). Conclusions: Ivermectin at sub-lethal concentrations inhibits the sporogony of P. falciparum in An. gambiae. These findings support the utility of ivermectin for P. falciparum transmission control.